End-capped polyisobutylene polyurethane

ABSTRACT

A polymeric material includes a polyisobutylene-polyurethane block copolymer. The polyisobutylene-polyurethane block copolymer includes soft segments, hard segments, and end groups. The soft segments include a polyisobutylene diol residue. The hard segments include a diisocyanate residue. The end groups are bonded by urea bonds to a portion of the diisocyanate residue. The end groups include a residue of a mono-functional amine.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a continuation of and claims priority to U.S.patent application Ser. No. 16/248,498, filed Jan. 15, 2019 and claimspriority to U.S. Provisional Application No. 62/618,262, filed Jan. 17,2018, both of which are herein incorporated by reference in theirentirety.

TECHNICAL FIELD

The present disclosure relates to polymeric materials. Morespecifically, the disclosure relates to polyisobutylene-polyurethaneblock copolymers, methods for making polyisobutylene-polyurethane blockcopolymers, and medical devices containing polyisobutylene-polyurethaneblock copolymers

BACKGROUND

Polymeric materials are widely used in the field of medical devices. Forexample, polymeric materials such as silicone rubber, polyurethane, andfluoropolymers are used as coating and/or insulating materials formedical leads, stents, catheters, and other devices.

Block copolymers are polymeric materials made of alternating sections ofpolymerized monomers. Polyisobutylene-polyurethane block copolymers arepolymeric materials with many unique physical and mechanical properties.Exemplary properties, which may be particularly desirable in the fieldof medical devices, include thermal stability, chemical resistance,biocompatibility, and gas impermeability, among others.

Incorporating polymeric materials into implantable medical devices maybe done by a variety of methods, depending on the specific application.In some applications, for example, for implantable lead bodies, thepolymeric material may be extruded at a temperature sufficient to causethe block copolymer to flow, but not high enough to cause the polymericmaterial to break down. That is, the material that forms the lead afterthe extrusion and cooling has largely the same structure as the originalpolymeric material.

In other applications, it may be desirable to employ solvent-basedprocessing to incorporate a polymeric material into an implantablemedical device. Solvent-based processing includes electrospraying,electrospinning, spray coating, dip coating, and force spinning.Essential to all solvent-based processing of polymeric materials is theability to bring the polymeric material into solution while retainingthe basic structure of the polymeric material.

SUMMARY

Example 1 is a polymeric material including apolyisobutylene-polyurethane block copolymer. Thepolyisobutylene-polyurethane block copolymer includes soft segments,hard segments, and end groups. The soft segments include apolyisobutylene diol residue. The hard segments include a diisocyanateresidue. The end groups are bonded by urea bonds to a portion of thediisocyanate residue. The end groups include a residue of amono-functional amine.

Example 2 is the polymeric material of Example 1, wherein themono-functional amine is a primary amine or a secondary amine.

Example 3 is the polymeric material of either of Examples 1 or 2,wherein the mono-functional amine includes a C₃ to C₃₀ aliphatic chain.

Example 4 is the polymeric material of any of Examples 1-3, wherein themono-functional amine is butylamine.

Example 5 is the polymeric material of any of Examples 1-4, wherein thesoft segments are present in the copolymer in an amount of about 40% toabout 70% by weight of the copolymer, and the hard segments are presentin the copolymer in an amount of about 30% to about 60% by weight of thecopolymer.

Example 6 is the polymeric material of any of Examples 1-5, wherein thediisocyanate residue includes 4,4′-methylene diphenyl diisocyanateresidue.

Example 7 is the polymeric material of any of Examples 1-6, wherein thehard segments further include a chain extender residue.

Example 8 is the polymeric material of Example 7, wherein the chainextender residue is 1,4-butanediol residue.

Example 9 is the polymeric material of any of Examples 1-8, wherein thesoft segments further include at least one of a polyether diol residue,a polyester diol residue, and a polycarbonate diol residue.

Example 10 is a medical device including the polymeric material of anyof Examples 1-9.

Example 11 is a method of making a polymeric material. The methodincludes heating a mixture of soft segment components and hard segmentcomponents to an elevated temperature to form a prepolymer, reacting achain extender with the prepolymer to form a polymer, and reacting anend capping agent with at least one of: the prepolymer and the polymerto form the polymeric material. The soft segment components include apolyisobutylene diol. The hard segment components include adiisocyanate. The end capping agent includes a mono-functional amine.

Example 12 is the method of Example 11, wherein the mono-functionalamine is a primary amine or a secondary amine.

Example 13 is the method of either of Examples 11 or 12, wherein themono-functional amine includes a C₃ to C₃₀ aliphatic chain.

Example 14 is the method of any of Examples 11-13, wherein themono-functional amine is butylamine.

Example 15 is the method of any of Examples 11-14, wherein thediisocyanate is in stoichiometric excess with respect to thepolyisobutylene diol and the chain extender, and the mono-functionalamine is an at least equimolar amount with respect to the diisocyanate.

Example 16 is a polymeric material including apolyisobutylene-polyurethane block copolymer. Thepolyisobutylene-polyurethane block copolymer includes soft segments,hard segments, and end groups. The soft segments include apolyisobutylene diol residue. The hard segments include a diisocyanateresidue. The end groups are bonded by urea bonds to a portion of thediisocyanate residue. The end groups include a residue of amono-functional amine including a C₃ to C₃₀ aliphatic chain.

Example 17 is the polymeric material of Example 16, wherein themono-functional amine is a primary amine or a secondary amine.

Example 18 is the polymeric material of Example of either of Examples 16or 17, wherein the mono-functional amine is butylamine.

Example 19 is the polymeric material of any of Examples 16-18, whereinthe soft segments are present in the copolymer in an amount of about 40%to about 70% by weight of the copolymer, and the hard segments arepresent in the copolymer in an amount of about 30% to about 60% byweight of the copolymer.

Example 20 is the polymeric material of any of Examples 16-19, whereinthe diisocyanate residue includes 4,4′-methylene diphenyl diisocyanateresidue.

Example 21 is the polymeric material of any of Examples 16-19, whereinthe hard segments further include a chain extender residue.

Example 22 is the polymeric material of Example 21, wherein the chainextender residue is 1,4-butanediol residue.

Example 23 is the polymeric material of any of Examples 16-22, whereinthe soft segments further include at least one of: a polyether diolresidue, a polyester diol residue, and a polycarbonate dial residue.

Example 24 a medical device including a polymeric material. Thepolymeric material includes a polyisobutylene-polyurethane blockcopolymer. The polyisobutylene-polyurethane block copolymer includessoft segments, hard segments, and end groups. The soft segments includea polyisobutylene diol residue. The hard segments include a diisocyanateresidue. The end groups are bonded by urea bonds to a portion of thediisocyanate residue. The end groups include a residue of amono-functional amine including a C₃ to C₃₀ aliphatic chain.

Example 25 is the medical device of Example 24, wherein themono-functional amine is a primary amine or a secondary amine.

Example 26 is the medical device of either of Examples 24 or 25, whereinthe mono-functional amine is butylamine.

Example 27 is the medical device of any of Examples 24-26, wherein thesoft segments are present in the copolymer in an amount of about 40% toabout 70% by weight of the copolymer, and the hard segments are presentin the copolymer in an amount of about 30% to about 60% by weight of thecopolymer.

Example 28 is the medical device of any of Examples 24-27, wherein thediisocyanate residue includes 4,4′-methylene diphenyl diisocyanateresidue.

Example 29 is a method of making a polymeric material. The methodincludes heating a mixture of soft segment components and hard segmentcomponents to an elevated temperature to form a prepolymer, reacting achain extender with the prepolymer to form a polymer, and reacting anend capping agent with at least one of: the prepolymer and the polymerto form the polymeric material. The soft segment components include apolyisobutylene diol. The hard segment components include adiisocyanate. The end capping agent includes a mono-functional amineincluding a C₃ to C₃₀ aliphatic chain.

Example 30 is the method of Example 29, wherein the mono-functionalamine is a primary amine or a secondary amine.

Example 31 is the method of either of Examples 29 or 30, wherein themono-functional amine is butylamine.

Example 32 is the method of any of Examples 29-31, wherein thediisocyanate is in stoichiometric excess with respect to thepolyisobutylene diol and the chain extender, and the mono-functionalamine is an at least equimolar amount with respect to the diisocyanate.

Example 33 is the method of any of Examples 29-32, wherein heating themixture of the soft segment components and the hard segment componentsto an elevated temperature and reacting the chain extender with theheated mixture are in the presence of a tertiary amine catalyst.

Example 34 is the method of Example 29, wherein the diisocyanateincludes 4,4′-methylene diphenyl diisocyanate.

Example 35 is the method of any of Examples 29-34, wherein the softsegment components further include a polytetramethylene oxide diol, thediisocyanate is in stoichiometric excess with respect to thepolyisobutylene diol, the chain extender, and the polytetramethyleneoxide diol, and the mono-functional amine is an at least equimolaramount with respect to the diisocyanate.

While multiple examples are disclosed, still other examples inaccordance with this disclosure will become apparent to those skilled inthe art from the following detailed description, which shows anddescribes illustrative embodiments. Accordingly, the drawings anddetailed description are to be regarded as illustrative in nature andnot restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram illustrating a first step of a process toproduce polyisobutylene-polyurethane according to some embodiments ofthis disclosure.

FIG. 2 is a schematic diagram illustrating a second step of a process toproduce polyisobutylene-polyurethane according to some embodiments ofthis disclosure.

FIG. 3 is a schematic diagram illustrating another process to producepolyisobutylene-polyurethane according to some embodiments of thisdisclosure.

FIG. 4 is a plot of dynamic viscosity as a function of concentration forpolyisobutylene-polyurethane solutions according to some embodiments ofthis disclosure.

While this disclosure is amenable to various modifications andalternative forms, specific embodiments have been shown by way ofexample in the drawings and are described in detail below. Theintention, however, is not to limit the disclosure to the particularembodiments described. On the contrary, this disclosure is intended tocover all modifications, equivalents, and alternatives falling withinthe scope of the disclosure as defined by the appended claims.

DETAILED DESCRIPTION

In accordance with various aspects of the disclosure,polyisobutylene-polyurethane block copolymers (also referred to hereincollectively as “PIB-PUR”) and methods for making the same aredisclosed. Medical devices that can be implantable or insertable intothe body of a patient and that comprise a polyisobutylene urethanecopolymer are also disclosed. PIB-PUR is a thermoplastic polyurethane(TPUs) that contains hard and soft segments. PIB-PUR is useful in anumber of applications, including in medical devices used for insertionor implantation into a patient because they are hydrolytically stableand have good oxidative stability.

Polyurethanes are a family of copolymers that are synthesized frompolyfunctional isocyanates (e.g., diisocyanates, including bothaliphatic and aromatic diisocyanates) and polyols (e.g., macroglycols).Commonly employed macroglycols include polyester diols, polyether diolsand polycarbonate diols. The macroglycols can form polymeric segments ofthe polyurethane. Aliphatic or aromatic diols may also be employed aschain extenders, for example, to impart improved physical properties tothe polyurethane.

In some embodiments, the polyisobutylene urethane copolymer includes oneor more polyisobutylene segments, one or more segments that includes oneor more diisocyanate residues, optionally one or more additionalpolymeric segments (other than polyisobutylene segments), and optionallyone or more chain extenders.

As used herein, a “polymeric segment” or “segment” is a portion of apolymer. The polyisobutylene segments of the polyisobutylene urethanecopolymers are generally considered to constitute soft segments, whilethe segments containing the diisocyanate residues are generallyconsidered to constitute hard segments. The additional polymericsegments may include soft or hard polymeric segments. As used herein,soft and hard segments are relative terms to describe the properties ofpolymer materials containing such segments. Without limiting theforegoing, a soft segment may display a glass transition temperature(Tg) that is below body temperature, more typically from 35° C. to 20°C. to 0° C. to −25° C. to −50° C. or below. A hard segment may display aTg that is above body temperature, more typically from 40° C. to 50° C.to 75° C. to 100° C. or above. Tg can be measured by differentialscanning calorimetry (DSC), dynamic mechanical analysis (DMA) and/orthermomechanical analysis (TMA).

The weight ratio of soft segments to hard segments in thepolyisobutylene urethane copolymers of the various embodiments can bevaried to achieve a wide range of physical and mechanical properties,and to achieve an array of desirable functional performance. Forexample, the weight ratio of soft segments to hard segments in thepolymer can be varied from 99:1 to 95:5 to 90:10 to 75:25 to 50:50 to25:75 to 10:90 to 5:95 to 1:99, more particularly from 95:5 to 90:10 to80:20 to 70:30 to 65:35 to 60:40 to 50:50, and even more particularly,from about 80:20 to about 50:50. In some embodiments, the soft segmentcomponents can be about 40% to about 70% by weight of the copolymer, andthe hard segment components can be about 30% to about 60% by weight ofthe copolymer.

In some embodiments, the copolymer may include polyisobutylene in anamount of about 60% to about 100% by weight of the soft segments and apolyether, a polyester, or a polycarbonate in an amount of about 0% toabout 40% by weight of the soft segments. For example, the copolymer mayinclude soft segments in an amount of about 40% to about 70% by weightof the copolymer, of which polyisobutylene is present in an amount ofabout 60% to about 100% by weight of the soft segments and polyether ispresent in an amount of about 0% to about 40% by weight of the softsegments. In another embodiment, the copolymer may include soft segmentsin an amount of about 40% to about 70% by weight of the copolymer, ofwhich polyisobutylene (e.g., a polyisobutylene diol residue) is presentin an amount of about 70% to about 95% by weight of the soft segmentsand a polyether (e.g., polytetramethylene oxide diol residue) is presentin an amount of about 5% to about 40% by weight of the soft segments.

Diisocyanates for use in forming PIB-PUR of the various embodimentsinclude aromatic and non-aromatic (e.g., aliphatic) diisocyanates.Aromatic diisocyanates may be selected from suitable members of thefollowing, among others: 4,4′-methylenediphenyl diisocyanate (MDI),2,4′-methylenediphenyl diisocyanate (2,4-MDI), 2,4- and/or 2,6-toluenediisocyanate (TDI), 1,5-naphthalene diisocyanate (NDI), para-phenylenediisocyanate, 3,3′-tolidene-4,4′-diisocyanate and3,3′-dimethyl-diphenylmethane-4,4′-diisocyanate. Non-aromaticdiisocyanates may be selected from suitable members of the following,among others: 1,6-hexamethylene diisocyanate (HDI),4,4′-dicyclohexylmethane diisocyanate (H12-MDI),3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate (isophoronediisocyanate or IPDI), cyclohexyl diisocyanate, and2,2,4-trimethyl-1,6-hexamethylene diisocyanate (TMDI).

In some embodiments, a polyether diol such as polytetramethylene oxidediol (PTMO diol), polyhexametheylene oxide diol (PHMO diol),polyoctamethylene oxide diol or polydecamethylene oxide diol, can becombined with a polyisobutylene diol and diisocyanate to form apolyisobutylene polyurethane copolymer. In some embodiments, PIB-PUR mayhave a generally uniform distribution of polyurethane hard segments,polyisobutylene segments and polyether segments to achieve favorablemicro-phase separation in the polymer. In some embodiments, polyethersegments may improve key mechanical properties such as Shore hardness,tensile strength, tensile modulus, flexural modulus, elongation tearstrength, flex fatigue, tensile creep, and/or abrasion performance,among others.

The polyisobutylene diol may be a telechelic polyisobutylene diol formedfrom by carbocationic polymerization beginning with a difunctionalinitiator compound, such as5-tert-butyl-1,3-bis(1-methoxy-1-methylethyl)benzene (hindered dicumylether).

PIB-PUR in accordance with the various embodiments may further includeone or more optional chain extender residues. Chain extenders canincrease the hard segment length, which can in turn results in acopolymer with a higher tensile modulus, lower elongation at breakand/or increased strength.

Chain extenders can be formed from aliphatic or aromatic diols, in whichcase a urethane bond is formed upon reaction with an isocyanate group.Chain extenders may be selected from suitable members of the following,among others: 1,4 cyclohexanedimethanol, alpha,omega-alkane diols suchas ethylene glycol (1,2-ethane diol), 1,4-butanediol (BDO), and1,6-hexanediol. Chain extenders may be also selected from suitablemembers of, among others, short chain diol polymers (e.g.,alpha,omega-dihydroxy-terminated polymers having a molecular weight lessthan or equal to 1000) based on hard and soft polymeric segments (moretypically soft polymeric segments) such as those described above,including short chain polyisobutylene diols, short chain polyetherpolyols such as polytetramethylene oxide diols, short chain polysiloxanediols such as polydimethylsiloxane dials, short chain polycarbonatediols such as polyhexamethylene carbonate diols, short chainpoly(fluorinated ether) diols, short chain polyester dials, short chainpolyacrylate dials, short chain polymethacrylate dials, and short chainpolyvinyl aromatic) dials. Chain extenders may also be selected formsuitable glycols, such as propylene glycol, dipropylene glycol, andtripropylene glycol.

As noted above, it may be desirable to employ solvent-based processingto incorporate a polymeric material, such as PIB-PUR, into animplantable medical device. In some embodiments, the PIB-PUR may besynthesized and stored for a period of time until it is incorporatedinto the solvent processing. For example, the FIB-PUR may be stored fora period of days, weeks or months. For solvent processing, the PIB-PURis dissolved in a solvent, such as, for example, 2,6-dimethylpyridine ortetrahydrofuran (THF), to obtain a desired concentration and/orviscosity of the resulting PIB-PUR solution. The PIB-PUR solution canthen be deposited onto a substrate, such as a medical device, byelectrospraying, electrospinning, spray coating, dip coating, or forcespinning.

It has been found that as PIB-PUR is stored for an extended period oftime, on the order of weeks and months, the molecular weight (both theweight average molecular weight (Mw) and the number average molecularweight (Mn)) of the PIB-PUR can increase during the storage period. Insome cases, the stored PIB-PUR forms a gel. Such gels are that is nolonger easily soluble in 2,6-dimethylpyridine or THF and thus, no longersuitable for solvent-based processing.

It has been found that, in some embodiments, an end-capping agent thatis a mono-functional amine can mitigate the increase in molecular weightdue to extended storage time. In addition, it has been found that, insome embodiments, the addition of such an end capping agent to PIB-PURthat has been stored for an extended period of time can reverse theincrease in molecular weight of the PIB-PUR. Further, it has been foundthat the addition of such an end capping agent to PIB-PUR even after ishas gelled and is no longer soluble in 2,6-dimethylpyridine or THF canbreak down the cross-links in the gel so that the PIB-PUR is soluble in2,6-dimethylpyridine or THF. A gel is defined as a substantially dilutecross-linked system which exhibits no flow when in a steady-state.

The mono-functional amine can include a C₃ to C₃₀ aliphatic chain thatcan be straight or branched, saturated or unsaturated, a primary amineor a secondary amine. For example, in some embodiments, themono-functional amine can be a butylamine or a butylamine ether, such as2-methoxy ethylamine.

FIG. 1 is a schematic diagram illustrating a first step of a process toproduce polyisobutylene-polyurethane according to some embodiments ofthis disclosure. A polymeric material including PIB-PUR according toembodiments of this disclosure can be made by mixing soft segmentcomponents 10, including polyisobutylene diol 12 and optional polyetherdiol 14 (PTMO is illustrated), and hard segment component 16, includinga diisocyanate 18 (MDI is illustrated), together and heating the mixtureto an elevated temperature in the presence of a catalyst 20 to form aprepolymer 22.

An elevated temperature is any temperature above room temperature, suchas 30° C., 40° C., 50° C., 60° C., 70° C., 80° C., 90° C., or 100° C.,or any temperature between any of the preceding temperatures. Thecatalyst can be any suitable catalyst, such as, an organometalliccatalyst, for example, tin(II) 2-ethylhexanoate (stannous octoate), or atertiary amine catalyst, for example, 2,6-dimethylpyridine,1-cyclohexyl-N,N-dimethylmethanamine,N,N,N′,N′,N″-pentamethyldiethylenetriamine, or 4-methylmorpholine,1-methylimidazole.

The second step is shown in FIG. 2 . A chain extender 24 (BDO isillustrated) is reacted at an elevated temperature with the prepolymer22, along with the mono-functional amine 26 (butylamine is illustrated)in the presence of the catalyst 20 to form a PIB-PUR 28. As shown inFIG. 2 , the mono-functional amine 26 caps the ends of the PIB-PUR 28,reacting with the diisocyanate 18 to prevent further chain extension.The mono-functional amine 26 may also react with excess diisocyanate 18and reduce unwanted side reactions. In some embodiments, themono-functional amine 26 may be added to the prepolymer 22 at the sametime as the chain extender 24. In other embodiments, the mono-functionalamine 26 may be added after the chain extender 24 has at least partiallyreacted with the prepolymer 22 to form a polymer. In some embodiments,the mono-functional amine 26 may be added to the prepolymer 22 at thesame time as the chain extender 24 and after the chain extender 24 hasat least partially reacted with the prepolymer 22 to form a polymer.

The diisocyanate 18 can be in stoichiometric excess with respect to thepolyisobutylene diol 12, the optional polyether diol 14, and the chainextender 24. The diisocyanate 18 may be in excess to account fordiisocyanate lost to reactions with residual water. For example, in someembodiments, the diisocyanate 18 is in excess with respect to thepolyisobutylene diol 12, the optional polyether 14, and the chainextender 24 by as little as 0.5 mole percent (mol %), 1 mol % 1.5 mol %,or 2 mol %, or as much as 2.5 mol %, 3 mol %, 4 mol %, or 5 mol %, orany value between any two of the preceding values. For example in someembodiments, the diisocyanate 18 is in excess with respect to thepolyisobutylene diol 12, the optional polyether 14, and the chainextender 24 by from 0.5 mol % to 5 mol %, 1 mol % to 4 mol %, 1.5 mol %to 3 mol %, 2 mol % to 2.5 mol %, or 0.5 mol % to 2.5 mol %.

In some embodiments, the mono-functional amine 26 can be added in atleast equimolar amounts with respect to the diisocyanate 18. In someembodiments, an excess of the mono-functional amine 26 can be added. Ifnecessary, some of the excess mono-functional amine 26 can be removed byheating above the boiling point of the mono-functional amine 26. Forexample, excess butylamine can be removed by heating above about 78° C.,the boiling point of butylamine.

Thus, the PIB-PUR 28 illustrated in FIG. 2 is a polymeric materialincluding at least soft segments including a residue of thepolyisobutylene diol 12, hard segments including at least residue of thediisocyanate 18, and end groups bonded to some of the diisocyanateresidue by a urea bond. The end groups are a residue of themono-functional amine 26. The hard segments of the embodiment shown inFIG. 2 further include a residue of the chain extender 24. The softsegments of the embodiment shown in FIG. 2 also further include aresidue of the polyether diol 14. In some embodiments, the soft segmentscan alternatively or additionally include a residue of a polycarbonatediol and/or a polyester diol.

FIG. 3 is a schematic diagram illustrating another process to producepolyisobutylene-polyurethane according to some embodiments of thisdisclosure. In the embodiment shown in FIG. 3 , the mono-functionalamine 26 (butylamine is shown) is added after the polymerizationreaction is at least substantially complete. The polymerization reactionis at least substantially complete when there is no noticeable increasein the viscosity of the polyisobutylene-polyurethane over a period ofseveral hours. FIG. 3 shows a PIB-PUR chain 30 and a diisocyanateresidue 32 bonded to a urethane linkage of the PIB-PUR 30 to form anallophanate 34. In some embodiments, the PIB-PUR 30 may have beenproduced and end-capped with a mono-functional amine as for PIB-PUR 28described above. In other embodiments, the PIB-PUR 30 may not have beenend-capped with a mono-functional amine when initially synthesized. Thediisocyanate residue 32 may be a result of the excess of diisocyanateused to make the PIB-PUR 30 as described above.

Without wishing to be bound by any theory, it is believed that duringstoring for an extended period of time, the diisocyanate residue 32 alsobonds with other hard or soft segment components, including other chainsof the PIB-PUR 30 (not shown), thus cross-linking the other hard or softsegment components to the PIB-PUR 30, increasing the molecular weight ofthe PIB-PUR 30, and eventually gelling the PIB-PUR 30 as describedabove. These side reactions can form the allophanate 34. Other sidereactions can form other cross-linking structures, such as a biuret (notshown).

The allophanate 34 is a reversible bond. As noted above, it has beenfound that the addition of the mono-functional amine 26, even after thePIB-PUR 30 has gelled, reverses the gelling of the PIB-PUR 30 andreduces its molecular weight. Without wishing to be bound by any theory,it is believed that the steric hindrance associated with the allophanate34 weakens the bond, resulting in the reversible bond shown in FIG. 3 .It is believed that the diisocyanate residue 32 bonds preferentiallywith the mono-functional amine 26, tying up the diisocyanate residue 32in a more stable alkyl amine 36 (a butyl amine shown), as shown in FIG.3 . Tying up the diisocyanate reside 32 may prevent reformation of theallophanate 34 and reduce the cross-linking of the other hard or softsegment components to the PIB-PUR 30, breaking down the gelation of thePIB-PUR 30 and reducing the molecular weight of the PIB-PUR 30. In someembodiments, the molecular weight of the PIB-PUR 30 may be reduced to aninitial molecular weight of a linear chain of PIB-PUR 30.

The amine termination of the mono-functional amine 26 is believed to bewell suited to this application, in contrast to, for example, asimilarly-structured mono-functional alcohol. It has been found thatwhile the mono-functional amine 26 is effective in reversing gelation ofthe PIB-PUR 30, a similarly-structured mono-functional alcohol is noteffective.

The PIB-PUR 26 or PIB-PUR 30 according to embodiments of this disclosurecan be incorporated into medical devices which can be implanted orinserted into the body of a patient. Example medical devices mayinclude, without limitation, vascular grafts, electrical leads,catheters, leadless cardiac pacemakers (LCP), pelvic floor repairsupport devices, shock coil coverings, covered stents, urethral stents,internal feeding tubes/balloons, structural heart applications includingvalve leaflets, suture sleeves, breast implants, ophthalmic applicationsincluding intraocular lenses and glaucoma tubes, and spinal disc repair.Example electrical leads may include, without limitation, implantableelectrical stimulation or diagnostic systems including neurostimulationsystems such as spinal cord stimulation (SCS) systems, deep brainstimulation (DBS) systems, peripheral nerve stimulation (PNS) systems,gastric nerve stimulation systems, cochlear implant systems, and retinalimplant systems, among others, and cardiac systems including implantablecardiac rhythm management (CRM) systems, implantablecardioverter-defibrillators (ICD's), and cardiac resynchronization anddefibrillation (CRDT) devices, among others.

EXAMPLES

The present disclosure is more particularly described in the followingexamples that are intended as illustrations only, since numerousmodifications and variations within the scope of the present disclosurewill be apparent to those of skill in the art. Unless otherwise noted,all parts, percentages, and ratios reported in the following examplesare on a weight bases, and all reagents used in the examples wereobtained, or are available, from the chemical suppliers described below,or may be synthesized by conventional techniques.

Example 1 PIB-PUR Treatment after 98 Days

Polyisobutylene-polyurethane block copolymer (PIB-PUR) including softsegments including a polyisobutylene diol residue and hard segmentsincluding a diisocyanate residue was prepared as follows. In a 1 literresin kettle, 106 grams of telechelic polyisobutylene diol formed fromby carbocationic polymerization beginning with5-feat-butyl-1,3-bis(1-methoxy-1-methylethyl)benzene, 72 grams of4′-methylenediphenyl diisocyanate (MDI), and 56 grams ofpolytetramethylene oxide diol were dissolved in 545 grams of2,6-dimethylpyridine. The 1 liter resin kettle was equipped withoverhead mechanical stirring and was purged with dry nitrogen gas. Thepolyisobutylene diol had a number average molecular weight (Mn) of 1905grams/mole and the polytetramethylene oxide diol had a Mn of 1000grams/mole. The solution was stirred by the overhead mechanical stirrerunder the flow of nitrogen gas at a temperature of 60 degrees Celsiuswhile the reagents reacted for 2 hours. After the 2 hours, 16 grams offreshly distilled 1,4-butanediol was added to the solution by dropwiseaddition and the solution maintained at a temperature of 70 degreesCelsius while the reaction continued for an additional 2 hours. Afterthe additional 2 hours, the solution was highly viscous solutioncontaining the PIB-PUR.

The PIB-PUR was stored at room temperature in a sealed container. After15 days, the PIB-PUR was characterized by gel permeation chromatographyusing a multi angle light scattering detector (GPC-MALLS) to determinethe number average molecular weight (Mn) and the weight averagemolecular weight (Mw). The PIB-PUR was recharacterized after 63 days and98 days. The results are shown in Table 1 below. As shown in Table 1 themolecular weight increased, particularly between 64 and 98 days. At 98days, the PIB-PUR was observed to have gelled. The gelled FIB-FUR wasfound to be predominantly insoluble in either 2,6-dimethylpyridine orTHF, indicating that chemical cross-linking of the PIB-PUR had occurred(the molecular weight was determined from a soluble fraction).

The gelled PIB-PUR was treated with butylamine in excess equimolarconcentration to the MDI by adding 2,6-dimethylpyridine and 0.5 g ofbutylamine to 1 g of the gelled PIB-PUR, and then shaking on a shakertable at 225 rpm at 30° C. for about 12 hours. The treated PIB-PURbecame a viscous liquid again indicating that whatever chemicalcross-linking had taken place appeared to have been reversed with theaddition of the butylamine. The treated PIB-PUR solution wasrecharacterized after 24 hours and after 25 days. The results are alsoshown in Table 1. As shown in Table 1, the molecular weight of thetreated PIB-PUR decreased significantly with the addition of thebutylamine.

TABLE 1 PIB-PUR Mn Mw After 15 days 128,100 286,100 After 63 days132,200 282,500 After 98 days 213,100 393,100 24 hours after 109,200259,700 Butylamine Treatment 25 days after 89,600 217,000 ButylamineTreatment

Example 2 PIB-PUR Treatment after 24 Days

Polyisobutylene-polyurethane block copolymer (PIB-PUR) including softsegments including a polyisobutylene diol residue and hard segmentsincluding a diisocyanate residue was prepared as follows. In a 1 literresin kettle, 105 grams of telechelic polyisobutylene diol formed fromby carbocationic polymerization beginning with5-tert-butyl-1,3-bis(1-methoxy-1-methylethyl)benzene, 72 grams of4′-methylenediphenyl diisocyanate (MDI), and 57 grams ofpolytetramethylene oxide diol were dissolved in 546 grams of2,6-dimethylpyridine. The 1 liter resin kettle was equipped withoverhead mechanical stirring and was purged with dry nitrogen gas. Thepolyisobutylene diol had a number average molecular weight (Mn) of 1905grams/mole and the polytetramethylene oxide diol had a Mn of 1000grams/mole. The solution was stirred by the overhead mechanical stirrerunder the flow of nitrogen gas at a temperature of 60 degrees Celsiuswhile the reagents reacted for 2 hours. After the 2 hours, 16 grams offreshly distilled 1,4-butanediol was added to the solution by dropwiseaddition and the solution maintained at a temperature of 70 degreesCelsius while the reaction continued for an additional 2 hours. Afterthe additional 2 hours, the solution was highly viscous solutioncontaining the PIB-PUR.

The PIB-PUR was stored at room temperature in a sealed container. ThePIB-PUR was characterized after 24 days by gel permeation chromatographyusing a multi angle light scattering detector (GPC-MALLS) to determinethe number average molecular weight (Mn) and the weight averagemolecular weight (Mw). The results are shown in Table 2 below.

The PIB-PUR was treated with butylamine in at least equimolarconcentration to the MDI by adding 2,6-dimethylpyridine and 0.08 g ofbutylamine to 1 g of the PIB-PUR, and then shaken on a shaker table at225 rpm at 30° C. for about 12 hours. The treated PIB-PUR solution wasstored at room temperature in a sealed container and recharacterizedafter 24 hours. The results are also shown in Table 2. As shown in Table2, the molecular weight of the treated PIB-PUR decreased significantlywith the addition of the butylamine suggesting that at least some of thechemical cross-linking that had taken place over 24 days appeared tohave been reversed with the addition of the butylamine.

TABLE 2 PIB-PUR Mn Mw After 24 days 138,700 313,600 24 hours after51,330 142,500 Butylamine Treatment

A dynamic viscosity was measured for various concentrations of thePIB-PUR of Example 2 in 2,6-dimethylpyridine before treatment 40 and 24hours after treatment 42 with the butylamine. Three PIB-PUR solutions ofvarious concentrations were prepared for each of the before treatment 40and after treatment 42 by adding appropriate amounts of2,6-dimethylpyridine. The results are shown in FIG. 4 . As shown in FIG.4 , the dynamic viscosity dropped significantly with the addition of thebutylamine, again suggesting that at least some of the chemicalcross-linking that had taken place over 24 days appeared to have beenreversed with the addition of the butylamine.

Example 3 PIB-PUR Treatment after 21 Days

Polyisobutylene-polyurethane block copolymer (PIB-PUR) including softsegments including a polyisobutylene diol residue and hard segmentsincluding a diisocyanate residue was prepared as follows. In a 1 literresin kettle 13 grams of telechelic polyisobutylene diol formed from bycarbocationic polymerization beginning with5-tert-butyl-1,3-bis(1-methoxy-1-methylethyl)benzene, 9 grams of4′-methylenediphenyl diisocyanate (MDI), and 7 grams ofpolytetramethylene oxide diol were dissolved in 8 grams of2,6-dimethylpyridine. The 1 liter resin kettle was equipped withoverhead mechanical stirring and was purged with dry nitrogen gas. Thepolyisobutylene diol had a number average molecular weight (Mn) of 1905grams/mole and the polytetramethylene oxide diol had a Mn of 1000grams/mole. The solution was stirred by the overhead mechanical stirrerunder the flow of nitrogen gas at a temperature of 60 degrees Celsiuswhile the reagents reacted for 2 hours. After the 2 hours, 2 grams offreshly distilled 1,4-butanediol was added to the solution by dropwiseaddition and the solution maintained at a temperature of 70 degreesCelsius while the reaction continued for an additional 2 hours. Afterthe additional 2 hours, the solution was highly viscous solutioncontaining the PIB-PUR.

The PIB-PUR was stored at room temperature in a sealed container. ThePIB-PUR was characterized after 21 days by gel permeation chromatographyusing a multi angle light scattering detector (GPC-MALLS) to determinethe number average molecular weight (Mn) and the weight averagemolecular weight (Mw). The results are shown in Table 3 below.

The PIB-PUR was treated with butylamine in at least equimolarconcentration to the MDI by adding 2,6-dimethylpyridine and 0.08 g ofbutylamine to 1 g of the PIB-PUR, and then shaken on a shaker table at225 rpm at 30° C. for about 12 hours. The treated PIB-PUR solution wasstored at room temperature in a sealed container and recharacterizedafter 24 hours and after 17 days. The results are also shown in Table 3.As shown in Table 3, the molecular weight of the treated PIB-PURdecreased significantly with the addition of the butylamine suggestingthat at least some of the chemical cross-linking that had taken placeover 21 days appeared to have been reversed with the addition of thebutylamine. As further shown in Table 3, the cross-links did notreappear over an additional 17 days of storage.

TABLE 3 PIB-PUR Mn Mw After 21 days 71,700 184,000 24 hours after 65,970159,000 Butylamine Treatment 17 days after 61,970 147,800 ButylamineTreatment

A dynamic viscosity was measured for various concentrations of theFIB-FUR of Example 2 in 2,6-dimethylpyridine before treatment 44 and 24hours after treatment 46 with the butylamine. Three PIB-PUR solutions ofvarious concentrations were prepared for each of the before treatment 40and after treatment 42 by adding appropriate amounts of2,6-dimethylpyridine. The results are shown in FIG. 4 . As shown in FIG.4 , the dynamic viscosity dropped significantly with the addition of thebutylamine, again suggesting that at least some of the chemicalcross-linking that had taken place over 24 days appeared to have beenreversed with the addition of the butylamine.

Various modifications and additions can be made to the embodimentsdiscussed without departing from the scope of this disclosure. Forexample, while the embodiments described above refer to particularfeatures, the scope of this disclosure also includes embodiments havingdifferent combinations of features and embodiments that do not includeall of the described features. Accordingly, the scope of this disclosureis intended to embrace all such alternatives, modifications, andvariations as fall within the scope of the claims, together with allequivalents thereof.

We claim:
 1. A polymeric material comprising: apolyisobutylene-polyurethane block copolymer including: soft segmentsincluding a polyisobutylene diol residue; hard segments including adiisocyanate residue; and end groups bonded by urea bonds to a portionof the diisocyanate residue, the end groups including a residue of amono-functional, primary amine having a C₃ to C₃₀ aliphatic straightchain.
 2. The polymeric material of claim 1, wherein the soft segmentsare present in the copolymer in an amount of about 40% to about 70% byweight of the copolymer, and the hard segments are present in thecopolymer in an amount of about 30% to about 60% by weight of thecopolymer.
 3. The polymeric material of claim 1, wherein thediisocyanate residue includes 4,4′-methylene diphenyl diisocyanateresidue.
 4. The polymeric material of claim 1, wherein the hard segmentsfurther include a chain extender residue.
 5. The polymeric material ofclaim 4, wherein the chain extender residue is 1,4-butanediol residue.6. The polymeric material of claim 1, wherein the soft segments furtherinclude at least one of: a polyether diol residue, a polyester dialresidue, and a polycarbonate dial residue.
 7. A medical devicecomprising: a polymeric material including: apolyisobutylene-polyurethane block copolymer including: soft segmentsincluding a polyisobutylene diol residue; hard segments including adiisocyanate residue; and end groups bonded by urea bonds to a portionof the diisocyanate residue, the end groups including a residue of amono-functional, primary amine having a C₃ to C₃₀ aliphatic straightchain.
 8. The medical device of claim 7, wherein the soft segments arepresent in the copolymer in an amount of about 40% to about 70% byweight of the copolymer, and the hard segments are present in thecopolymer in an amount of about 30% to about 60% by weight of thecopolymer.
 9. The medical device of claim 7, wherein the diisocyanateresidue includes 4,4′-methylene diphenyl diisocyanate residue.
 10. Amethod of making a polymeric material, the method comprising: heating amixture of soft segment components and hard segment components to anelevated temperature, the soft segment components including apolyisobutylene diol, and the hard segment components including adiisocyanate to form a prepolymer; reacting a chain extender with theprepolymer to form a polymer; and reacting an end capping agent with atleast one of: the prepolymer and the polymer to form the polymericmaterial, wherein the end capping agent is a mono-functional, primaryamine having a C₃ to C₃₀ aliphatic straight chain.
 11. The method ofclaim 10, wherein the diisocyanate is in stoichiometric excess withrespect to the polyisobutylene diol and the chain extender, and themono-functional amine is in at least equimolar amount with respect tothe diisocyanate.
 12. The method of claim 10, wherein heating themixture of the soft segment components and the hard segment componentsto an elevated temperature and reacting the chain extender with theheated mixture are in the presence of a tertiary amine catalyst.
 13. Themethod of claim 10, wherein the diisocyanate includes 4,4′-methylenediphenyl diisocyanate.
 14. The method of claim 10, wherein the softsegment components further include a polytetramethylene oxide diol, thediisocyanate is in stoichiometric excess with respect to thepolyisobutylene diol, the chain extender, and the polytetramethyleneoxide diol, and the mono-functional amine is in at least equimolaramount with respect to the diisocyanate.
 15. The method of claim 10,wherein the end capping agent is reacted with the prepolymer to form thepolymeric material.
 16. The method of claim 10, wherein the end cappingagent is reacted with the polymer to form the polymeric material.